Striated muscle is the responsible for movement in animals and is composed of muscle fibers. These are generally classified into two main types: slow- and fast-twitch. The first one is designed for continuous, extended muscle contraction over a long time period, while the latter is designed for short bursts of strength. The composition of muscle fibers is tightly regulated to enable an organism to respond and adapt to changing physical demands. Accordingly, the formation of slow-twitch muscle fiber is promoted and regulated by the protein phosphatase calcineurin and its downstream targets, such as the nuclear factor of activated T cells (NFAT). In addition, it is well known that calcineurin is inhibited by sarcomeric Z-disc protein FATZ-1, also known as myozenin-1 or calsarcin-2, and as a consequence, FATZ-1-null mice exhibit an excess of slow-twitch muscle fibers (Frey et al. 2008; Seto et al. 2013). Although the mechanism by which calcineurin is inhibited by FATZ-1 has been characterized in detail in mice, very little is known about their interaction at the molecular level.
We are looking for a highly motivated and dedicated student to use an integrative structural biology approach to investigate calcineurin inhibition by FATZ-1 at the molecular level. The successful candidate will have the opportunity to (i) combine X-ray crystallography and SAXS to generate a structural model of the complexand (ii) use biochemical and biophysical methods to validate the mechanistic model.
Studies of Molecular Biology, Biochemistry, Cell Biology, Chemistry or related field. Interested students, please send CV and motivation letter to email@example.com
Kristina Djinovic Carugo
Dept of Structural and Computational Biology
Max Perutz Labs
University of Vienna
Campus Vienna Biocenter 5, A-1030 Vienna
Frey et al. “Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activation”. J Clin. Invest.(2008)118: 3598-3608
Seto et al. “ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling”. J Clin. Invest.(2013)123: 4255-4263